Anomalous segregation dynamics of self-propelled particles

A number of novel experimental and theoretical results have recently been obtained on active soft matter, demonstrating the various interesting universal and anomalous features of this kind of driven systems. Here we consider a fundamental but still unexplored aspect of the patterns arising in the system of actively moving units, i.e., their segregation taking place when two kinds of them with different adhesive properties are present. The process of segregation is studied by a model made of self-propelled particles such that the particles have a tendency to adhere only to those which are of the same kind. The calculations corresponding to the related differential equations can be made in parallel, thus a powerful GPU card allows large scale simulations. We find that the segregation kinetics is very different from the non-driven counterparts and is described by the new scaling exponents $z\simeq 1$ and $z\simeq 0.8$ for the 1:1 and the non-equal ratio of the two constituents, respectively. Our results are in agreement with a recent observation of segregating tissue cells \emph{in vitro}

Collective behavior of interacting self-propelled particles

We discuss biologically inspired, inherently non-equilibrium self-propelled particle models, in which the particles interact with their neighbours by choosing at each time step the local average direction of motion. We summarize some of the results of large scale simulations and theoretical approaches to the problem

Az embrionális érhálózat önszerveződése = Self-organization of the embryonic vascular network

Kutatásaink az önszervezően, sok hasonló sejt kölcsönhatása révén létrejövő biológiai rendszerek, ezen belül elsősorban az embriófejlődés során kialakuló érhálózat és extracelluláris mátrix (ECM) tulajdonságainak vizsgálatára irányultak. A kutatómunka szerves része volt a sejtek viselkedésének megfigyelését lehetővé tevő mikroszkópos és statisztikai elemzés technikák kidolgozása is. Bevezettünk, és madárembriókon végzett kísérletekkel alátámasztottuk a fejlődő szöveteknek egy olyan képét, amelyben a szövet deformációira szuperponálódik a szövetbe ágyazott sejtek aktív (és korrelálatlanabb) mozgása. Megmutattuk, hogy a kezdeti érhálózat -- számos korábbi elképzeléssel ellentétben -- egy, az axonnövekedéshez nagyon hasonló sejtinvázióval történik. Sejttenyészetek in vitro viselkedésének analizálásával rámutattunk, hogy a lineáris szegmensek kialakításának egyik fontos mozgatóeleme a sejtek megváltozott mozgása erősen anizotróp környezetben. Ezekre az emprikus megfigyeléseinkre alapozva felállítottuk a vaszkulogenezis egy új elméleti modelljét. Feltérképeztük a korai embriogenezist jellemző szövetmozgásokat madárembriókban. Megmutattuk, hogy a gasztruláció folyamatát kísérő szövetmozgások jól leírhatók egy olyan tovaterjedő mintázatként, ami az embrió mindkét oldalán egy-egy, ellentétes irányban forgó örvényt tartalmaz. Mint a szövetalkotás egyik fő lépését, elemeztük a sejt-ECM kölcsönhatások szerepét a mintázatképzésben. | The research investigated self-organization phenomena in multicellular systems, especially the formation of blood vessel network during embryogenesis. Improvements in automatic microscopy techniques as well as image processing algorithms were also integral part of the research. Based on experimental analysis of delepoing bird embryos we introduced a mechanicl framwork desribing embryonic tissues, where cell autonomous motion is superimposed upon large-scale (convective) tissue movements. We showed that the early vascular network forms through a multicellular sprouting proess, somewhat reminescent to axon growth. Using in vitro cell cultures we showed that the formation of linear segment is a consequence of altered cell behavior in anisotropic environments. Based on these observations, we created a new theoretical model for vasculogenesis. We also mapped the large-scale tissue movements during embryogenesis. In bird embryos tissue movements during gastrulation form a travelling wave-like pattern containing a vortex on either side of the embryo. As a crucial step during tissue formation, we analyzed cell motion-mediated patterning of the extracellular matrix

Collective motion of organisms in three dimensions

We study a model of flocking in order to describe the transitions during the collective motion of organisms in three dimensions (e.g., birds). In this model the particles representing the organisms are self-propelled, i.e., they move with the same absolute velocity. In addition, the particles locally interact by choosing at each time step the average direction of motion of their neighbors and the effects of fluctuations are taken into account as well. We present the first results for large scale flocking in the presence of noise in three dimensions. We show that depending on the control parameters both disordered and long-range ordered phases can be observed. The corresponding phase diagram has a number of features which are qualitatively different from those typical for the analogous equilibrium models.Comment: 3 pages, 4 figure

Enhanced endothelial motility and multicellular sprouting is mediated by the scaffold protein TKS4

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Matrigel patterning reflects multicellular contractility

Non-muscle myosin II (NMII)-induced multicellular contractility is essential for development, maintenance and remodeling of tissue morphologies. Dysregulation of the cytoskeleton can lead to birth defects or enable cancer progression. We demonstrate that the Matrigel patterning assay, widely used to characterize endothelial cells, is a highly sensitive tool to evaluate cell contractility within a soft extracellular matrix (ECM) environment. We propose a computational model to explore how cellexerted contractile forces can tear up the cell-Matrigel composite material and gradually remodel it into a network structure. We identify measures that are characteristic for cellular contractility and can be obtained from image analysis of the recorded patterning process. The assay was calibrated by inhibition of NMII activity in A431 epithelial carcinoma cells either directly with blebbistatin or indirectly with Y27632 Rho kinase inhibitor. Using Matrigel patterning as a bioassay, we provide the first functional demonstration that overexpression of S100A4, a calcium-binding protein that is frequently overexpressed in metastatic tumors and inhibits NMIIA activity by inducing filament disassembly, effectively reduces cell contractility

Novel type of phase transition in a system of self-driven particles

A simple model with a novel type of dynamics is introduced in order to investigate the emergence of self-ordered motion in systems of particles with biologically motivated interaction. In our model particles are driven with a constant absolute velocity and at each time step assume the average direction of motion of the particles in their neighborhood with some random perturbation ($\eta$) added. We present numerical evidence that this model results in a kinetic phase transition from no transport (zero average velocity, $| {\bf v}_a | =0$) to finite net transport through spontaneous symmetry breaking of the rotational symmetry. The transition is continuous since $| {\bf v}_a |$ is found to scale as $(\eta_c-\eta)^\beta$ with $\beta\simeq 0.45$

Topography of Extracellular Matrix Mediates Vascular Morphogenesis and Migration Speeds in Angiogenesis

The extracellular matrix plays a critical role in orchestrating the events necessary for wound healing, muscle repair, morphogenesis, new blood vessel growth, and cancer invasion. In this study, we investigate the influence of extracellular matrix topography on the coordination of multi-cellular interactions in the context of angiogenesis. To do this, we validate our spatio-temporal mathematical model of angiogenesis against empirical data, and within this framework, we vary the density of the matrix fibers to simulate different tissue environments and to explore the possibility of manipulating the extracellular matrix to achieve pro- and anti-angiogenic effects. The model predicts specific ranges of matrix fiber densities that maximize sprout extension speed, induce branching, or interrupt normal angiogenesis, which are independently confirmed by experiment. We then explore matrix fiber alignment as a key factor contributing to peak sprout velocities and in mediating cell shape and orientation. We also quantify the effects of proteolytic matrix degradation by the tip cell on sprout velocity and demonstrate that degradation promotes sprout growth at high matrix densities, but has an inhibitory effect at lower densities. Our results are discussed in the context of ECM targeted pro- and anti-angiogenic therapies that can be tested empirically